Humans, livestock and pets often are vaccinated to prevent disease, or reduce the severity of disease. Vaccination results in the production of antibodies, which are serum proteins capable of binding specifically to antigen substances used in the vaccine. This humoral response involves the selection of specific lines of B lymphocytes, and the proliferation and differentiation of the selected cells to yield clones of antibody-producing plasma cells.
Antibody production reaches a peak within several weeks after immunization, and then gradually declines. Because of a constant turnover of serum proteins, the decline in antibody production is accompanied by a corresponding decline in the circulating level of antibodies. However, if the patient is challenged again with the same antigen, a new response curve is initiated more rapidly and more intensely than the first one. This is called a secondary, booster, or anamnestic response, and in healthy patients results in much higher antibody levels with higher affinity to the antigen than the first exposure, or primary immunization. The increased rate of antibody synthesis is the result of an increased number of antibody-producing plasma cells. These cells are scarce in the lymph nodes of the unimmunized patient, which contain mostly small lymphocytes. However, in healthy patients, plasma cells constitute up to 3% of the total lymph node cells after a primary immunization, and as much as 30% of the lymph node cells after a secondary immunization.
The secondary response is said to be due to immunological memory. That is, the healthy organism is able to “remember” its prior exposure to the antigen, and react more promptly and efficiently the second time it is exposed, even if the amount of specific antibodies in the serum has declined to a very low level in the meantime.
Certain conditions such as aging, malnutrition, drug addiction, alcoholism, and certain disease states such as diabetes, chronic renal disease, and AIDS, lead to immunodeficiency (e.g., an immunocompromised subject), in which many immune responses are quenched and vaccination is of reduced effectiveness. Thus, there remains a need in the art for improved vaccines and methods of vaccination, and in particular, for immune deficient patients.
Several administrations of TA1 to patients has shown some promise for enhancing immunity in connection with vaccination. For example, McConnell et al. (The Gerontologist 29:188 A (1989)) show that TA1 injections given twice weekly to elderly patients, for a total of eight injections, enhances antibody production in response to influenza vaccination. Shen et al. (Kidney International 31:217 (1987)) show that 5 injections of TA1 to hemodialysis patients (previously non-responsive to hepatitis B vaccination), can enhance antibody response to hepatitis B vaccination. However, a more convenient, efficient, and cost effective strategy for enhancing vaccine effectiveness is desirable.